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Loss of ovarian function and the risk of ovarian cancer

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Abstract

Animal models with premature ovarian failure resulting from the loss or depletion of germ cells consistently develop ovarian surface epithelial cell hyperplasia with invasion into the stroma and the development of ovarian tubular adenomas. In human ovaries, deep epithelial invaginations and inclusion cysts occur at increasing frequency with age and are thought to be the structures from which the majority of ovarian cancers arise. A feature that is common to these animal models and to post-menopausal women is a deficiency in the number of oocytes. The potential consequences of the loss or depletion of female germ cells, naturally or otherwise, include failure of follicle development, significant reductions in oestrogen and progesterone levels and elevation of circulating levels of gonadotropins. This review will consider the way in which these structural and hormonal changes affect ovarian cancer risk. Some lessons may be learned from gonad formation, since notable similarities exist between ovarian tumorigenesis and embryonic gonadogenesis including fragmentation of the basement membrane underlying the coelomic (surface) epithelium, the potential for the migration of epithelial cells into the gonad and the importance of the germ cells for the regulation of ovarian structure and function.

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Acknowledgements

The author thanks Dr. Douglas Gray for his critical review of this manuscript, Tanya Shaw for helpful discussions during its preparation, and Lisa Vandermeer and Dr. Jean-François Ethier for providing the micrographs in Figs. 1 and 2, respectively. The gdf9-deficient mice were generously provided by Dr. Martin Matzuk.

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Authors and Affiliations

  1. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada

    Barbara C. Vanderhyden

  2. Department of Obstetrics and Gynaecology, University of Ottawa, Ottawa, Ontario, Canada

    Barbara C. Vanderhyden

  3. Centre for Cancer Therapeutics, Ottawa Regional Cancer Centre, 503 Smyth Road, 3rd Floor, Ottawa, Ontario, K1H 1C4, Canada

    Barbara C. Vanderhyden

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  1. Barbara C. Vanderhyden
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Correspondence to Barbara C. Vanderhyden.

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Research was supported by grants from the National Cancer Institute of Canada and the Canadian Institutes of Health Research.

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Vanderhyden, B.C. Loss of ovarian function and the risk of ovarian cancer. Cell Tissue Res 322, 117–124 (2005). https://doi.org/10.1007/s00441-005-1100-1

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